The series was created by Ryan Murphy, Brad Falchuk, and Ian Brennan, the same trio behind Glee, and was originally ordered as a 15-episode season before being reduced to 13 episodes.

Ryan Murphy conceived the show like an Agatha Christie 'Ten Little Indians' structure, where a cast member is killed off each episode and viewers get clues to the killer's identity, with the killer's reveal saved for the season finale.

Co-creator Brad Falchuk said the writers decided on the killer's identity from the very beginning of the process and kept careful track of every attack to make sure no clues accidentally ruled out a suspect.

Joe Manganiello was originally cast in a main role but had to leave the series on March 13, 2015, due to promotional obligations for the film Magic Mike XXL, and was replaced by Oliver Hudson.

Brad Falchuk revealed that the writers considered sparing the actress playing 'Deaf Taylor Swift' from being killed off because they enjoyed working with her so much, but ultimately decided to proceed as planned to fit the story.

Principal photography began on March 12, 2015 in New Orleans, with exterior campus scenes shot at Tulane University standing in for the fictional Wallace University; the pilot wrapped in April 2015 before the rest of season one resumed filming in June 2015.

For season two, production moved from New Orleans to Los Angeles after securing a significant tax credit, with the setting changing from a university to a hospital.

Jamie Lee Curtis filmed a shot-for-shot homage to her mother Janet Leigh's iconic shower scene from Psycho; Curtis insisted on recreating it exactly, bought out a greeting card company's image of her mother screaming to keep near the monitor, and rewatched the original scene repeatedly to match tiny details like hand placement and eye twitches.

Scream queen Heather Langenkamp, known for her role in A Nightmare on Elm Street, worked on the special effects for the series.

The show's title sequence, designed by Kyle Cooper as a tribute to 1980s horror films, featured an original song called 'You Belong to Me' performed by Heather Heywood and written by composer Mac Quayle, Heywood, and executive producer Alexis Martin Woodall; it only appeared once, in episode five ('Pumpkin Patch'), trimmed to under a minute.